Systems and methods for real time tracking of targets in radiation therapy and other medical applications

ABSTRACT

Systems and methods for tracking targets in real time for radiation therapy and other applications. In one embodiment, a method includes collecting position information of a marker implanted within a patient at a site relative to the target at a time t n , and providing an objective output indicative of the location of the target based on the position information collected at time t n . The objective output is provided to a memory device, user interface, and/or radiation delivery machine within 1 ms to 2 seconds of the time t n  when the position information was collected. This embodiment of the method can further include providing the objective output at a periodicity of 10-200 ms during at least a portion of a treatment procedure. For example, the method can further include generating a beam of ionizing radiation and directing the beam to a machine isocenter, and continuously repeating the collecting procedure and the providing procedure every 10-200 ms while irradiating the patient with the ionizing radiation beam.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of U.S. ProvisionalApplication No. 60/610,509 filed on Sep. 16, 2004, and U.S. ProvisionalApplication No. 60/590,894 filed on Jul. 23, 2004, both of which areincorporated herein by reference in their entireties.

TECHNICAL FIELD

This invention relates generally to radiation therapy systems, and moreparticularly to systems and methods for accurately locating and trackinga target in real time for guiding and assessing radiation therapy. Theinvention, however, is also useful in other medical applications.

BACKGROUND OF THE INVENTION

Radiation therapy has become a significant and highly successful processfor treating prostate cancer, lung cancer, brain cancer and many othertypes of localized cancers. Radiation therapy procedures generallyinvolve (a) planning processes to determine the parameters of theradiation (e.g., dose, shape, etc.), (b) patient setup processes toposition the target at a desired location relative to the radiationbeam, (c) radiation sessions to irradiate the cancer, and (d)verification processes to assess the efficacy of the radiation sessions.Many radiation therapy procedures require several radiation sessions(i.e., radiation fractions) over a period of approximately 5-45 days.

To improve the treatment of localized cancers with radiotherapy, it isgenerally desirable to increase the radiation dose because higher dosesare more effective at destroying most cancers. Increasing the radiationdose, however, also increases the potential for complications to healthytissues. The efficacy of radiation therapy accordingly depends on boththe total dose of radiation delivered to the tumor and the dose ofradiation delivered to normal tissue adjacent to the tumor. To protectthe normal tissue adjacent to the tumor, the radiation should beprescribed to a tight treatment margin around the target such that onlya small volume of healthy tissue is irradiated. For example, thetreatment margin for prostate cancer should be selected to avoidirradiating rectal, bladder and bulbar urethral tissues. Similarly, thetreatment margin for lung cancer should be selected to avoid irradiatinghealthy lung tissue or other tissue. Therefore, it is not only desirableto increase the radiation dose delivered to the tumor, but it alsodesirable to mitigate irradiating healthy tissue.

One difficulty of radiation therapy is that the target often moveswithin the patient either during or between radiation sessions. Forexample, the prostate gland moves within the patient during radiationtreatment sessions because of respiration motion and/or organfilling/emptying (e.g., full or empty bladder). Tumors in the lungs alsomove during radiation sessions because of respiration motion and cardiacfunctions (e.g., heartbeats and vasculature constriction/expansion). Tocompensate for such movement, the treatment margins are generally largerthan desired so that the tumor does not move out of the treatmentvolume. This is not a desirable solution because the larger treatmentmargins may irradiate a larger volume of normal tissue.

Another challenge in radiation therapy is accurately aligning the tumorwith the radiation beam. Current setup procedures generally alignexternal reference markings on the patient with visual alignment guidesfor the radiation delivery device. For an example, a tumor is firstidentified within the patient using an imaging system (e.g., X-ray,computerized tomography (CT), magnetic resonance imaging (MRI), orultrasound system). The approximate location of the tumor relative totwo or more alignment points on the exterior of the patient is thendetermined. During setup, the external marks are aligned with areference frame of the radiation delivery device to position thetreatment target within the patient at the beam isocenter of theradiation beam (also referenced herein as the machine isocenter).Conventional setup procedures using external marks are generallyinadequate because the target may move relative to the external marksbetween the patient planning procedure and the treatment session and/orduring the treatment session. As such, the target may be offset from themachine isocenter even when the external marks are at theirpredetermined locations for positioning the target at the machineisocenter. Reducing or eliminating such an offset is desirable becauseany initial misalignment between the target and the radiation beam willlikely cause normal tissue to be irradiated. Moreover, if the targetmoves during treatment because of respiration, organ filling, or cardiacconditions, any initial misalignment will likely further exacerbateirradiation of normal tissue. Thus, the day-by-day and moment-by-momentchanges in target motion have posed significant challenges forincreasing the radiation dose applied to patients.

Conventional setup and treatment procedures using external marks alsorequire a direct line-of-sight between the marks and a detector. Thisrequirement renders these systems useless for implanted markers ormarkers that are otherwise in the patient (i.e., out of theline-of-sight of the detector and/or the light source). Thus,conventional optical tracking systems have many restrictions that limittheir utility in medical applications.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side elevation view of a tracking system for use inlocalizing and monitoring a target in accordance with an embodiment ofthe present invention. Excitable markers are shown implanted in oradjacent to a target in the patient.

FIG. 2 is a schematic elevation view of the patient on a movable supporttable and of markers implanted in the patient.

FIG. 3 is a side view schematically illustrating a localization systemand a plurality of markers implanted in a patient in accordance with anembodiment of the invention.

FIG. 4 is a flow diagram of an integrated radiation therapy process thatuses real time target tracking for radiation therapy in accordance withan embodiment of the invention.

FIG. 5A is a representation of a CT image illustrating an aspect of asystem and method for real time tracking of targets in radiation therapyand other medical applications.

FIG. 5B is a diagram schematically illustrating a reference frame of aCT scanner.

FIG. 6 is a screenshot of a user interface for displaying an objectiveoutput in accordance with an embodiment of the invention.

FIG. 7 is an isometric view of a radiation session in accordance with anembodiment of the invention.

FIG. 8A is an isometric view of a marker for use with a localizationsystem in accordance with an embodiment of the invention.

FIG. 8B is a cross-sectional view of the marker of FIG. 8A taken alongline 8B-8B.

FIG. 8C is an illustration of a radiographic image of the marker ofFIGS. 8A-8B.

FIG. 9A is an isometric view of a marker for use with a localizationsystem in accordance with another embodiment of the invention.

FIG. 9B is a cross-sectional view of the marker of FIG. 9A taken alongline 9B-9B.

FIG. 10A is an isometric view of a marker for use with a localizationsystem in accordance with another embodiment of the invention.

FIG. 10B is a cross-sectional view of the marker of FIG. 10A taken alongline 10B-10B.

FIG. 11 is an isometric view of a marker for use with a localizationsystem in accordance with another embodiment of the invention.

FIG. 12 is an isometric view of a marker for use with a localizationsystem in accordance with yet another embodiment of the invention.

FIG. 13 is a schematic block diagram of a localization system for use intracking a target in accordance with an embodiment of the invention.

FIG. 14 is a schematic view of an array of coplanar source coilscarrying electrical signals in a first combination of phases to generatea first excitation field.

FIG. 15 is a schematic view of an array of coplanar source coilscarrying electrical signals in a second combination of phases togenerate a second excitation field.

FIG. 16 is a schematic view of an array of coplanar source coilscarrying electrical signals in a third combination of phases to generatea third excitation field.

FIG. 17 is a schematic view of an array of coplanar source coilsillustrating a magnetic excitation field for energizing markers in afirst spatial orientation.

FIG. 18 is a schematic view of an array of coplanar source coilsillustrating a magnetic excitation field for energizing markers in asecond spatial orientation.

FIG. 19A is an exploded isometric view showing individual components ofa sensor assembly for use with a localization system in accordance withan embodiment of the invention.

FIG. 19B is a top plan view of a sensing unit for use in the sensorassembly of FIG. 19A.

FIG. 20 is a schematic diagram of a preamplifier for use with the sensorassembly of FIG. 19A.

FIG. 21 is a graph of illustrative tumor motion ellipses fromexperimental phantom based studies of the system.

FIG. 22 is a graph of root mean square (RMS) error from experimentalphantom based studies of the system.

FIG. 23 is an exemplary histogram of localization error fromexperimental phantom based studies of the system.

FIG. 24 is graph of position error as a function of speed fromexperimental phantom based studies of the system.

In the drawings, identical reference numbers identify similar elementsor components. The sizes and relative positions of elements in thedrawings are not necessarily drawn to scale. For example, the shapes ofvarious elements and angles are not drawn to scale, and some of theseelements are arbitrarily enlarged and positioned to improve drawinglegibility. Further, the particular shapes of the elements as drawn, arenot intended to convey any information regarding the actual shape of theparticular elements, and have been solely selected for ease ofrecognition in the drawings.

DETAILED DESCRIPTION

In the following description, certain specific details are set forth inorder to provide a thorough understanding of various embodiments of theinvention. However, one skilled in the relevant art will recognize thatthe invention may be practiced without one or more of these specificdetails, or with other methods, components, materials, etc. In otherinstances, well-known structures associated with target locating andtracking systems have not been shown or described in detail to avoidunnecessarily obscuring descriptions of the embodiments of theinvention.

Unless the context requires otherwise, throughout the specification andclaims which follow, the word “comprise” and variations thereof, suchas, “comprises” and “comprising” are to be construed in an open,inclusive sense that is as “including, but not limited to.”

Reference throughout this specification to “one embodiment” or “anembodiment” means that a particular feature, structure or characteristicdescribed in connection with the embodiment is included in at least oneembodiment of the present invention. Thus, the appearances of thephrases “in one embodiment” or “in an embodiment” in various placesthroughout this specification are not necessarily all referring to thesame embodiment. Further more, the particular features, structures, orcharacteristics may be combined in any suitable manner in one or moreembodiments.

The headings provided herein are for convenience only and do notinterpret the scope or meaning of the claimed invention.

A. Overview

FIGS. 1-24 illustrate a system and several components for locating,tracking and monitoring a target within a patient in real time inaccordance with embodiments of the present invention. The system andcomponents guide and control the radiation therapy to more effectivelytreat the target. Several embodiments of the systems described belowwith reference to FIGS. 1-24 can be used to treat targets in the lung,prostate, head, neck, breast and other parts of the body in accordancewith aspects of the present invention. Additionally, the markers andlocalization systems shown in FIGS. 1-24 may also be used in surgicalapplications or other medical applications. Like reference numbers referto like components and features throughout the various figures.

Several embodiments of the invention are directed towards methods fortracking a target, i.e., measuring the position and/or the rotation of atarget in substantially real time, in a patient in medical applications.One embodiment of such a method comprises collecting position data of amarker that is substantially fixed relative to the target. Thisembodiment further includes determining the location of the marker in anexternal reference frame (i.e., a reference frame outside the patient)and providing an objective output in the external reference frame thatis responsive to the location of the marker. The objective output isrepeatedly provided at a frequency/periodicity that adequately tracksthe location of the target in real time within a clinically acceptabletracking error range. As such, the method for tracking the targetenables accurate tracking of the target during diagnostic, planning,treatment or other types of medical procedures. In many specificapplications, the objective output is provided within a suitably shortlatency after collecting the position data and at a sufficiently highfrequency to use the data for such medical procedures.

Another specific embodiment is a method for treating a target in apatient with an ionizing radiation beam that includes collectingposition information of a marker implanted within a patient at a siterelative to the target at a time t_(n), and providing an objectiveoutput indicative of the location of the target based on the positioninformation collected at time t_(n). The objective output is provided toa memory device, user interface, and/or radiation delivery machinewithin 2 seconds or less of the time t_(n) when the position informationwas collected. This embodiment of the method can further includeproviding the objective output at a periodicity of 2 seconds or lessduring at least a portion of a treatment procedure. For example, themethod can further include generating a beam of ionizing radiation anddirecting the beam to a machine isocenter, and continuously repeatingthe collecting procedure and the providing procedure every 10-200 mswhile irradiating the patient with the ionizing radiation beam.

Another embodiment of a method for tracking a target in a patientincludes obtaining position information of a marker situated within thepatient at a site relative to the target, and determining a location ofthe marker in an external reference frame based on the positioninformation. This embodiment further includes providing an objectiveoutput indicative of the location of the target to a user interface at(a) a sufficiently high frequency so that pauses in representations ofthe target location at the user interface are not readily discernable bya human, and (b) a sufficiently low latency to be at least substantiallycontemporaneous with obtaining the position information of the marker.

Another embodiment of the invention is directed toward a method oftreating a target of a patient with an ionizing radiation beam bygenerating a beam of ionizing radiation and directing the beam relativeto the target. This method further includes collecting positioninformation of a marker implanted within the patient at a site relativeto the target while directing the beam toward the beam isocenter.Additionally, this method includes providing an objective outputindicative of a location of the target relative to the beam isocenterbased on the collected position information. This method can furtherinclude correlating the objective output with a parameter of the beam,and controlling the beam based upon the objective output. For example,the beam can be gated to only irradiate the patient when the target iswithin a desired irradiation zone. Additionally, the patient can bemoved automatically and/or the beam can be shaped automaticallyaccording to the objective output to provide dynamic control in realtime that maintains the target at a desired position relative to thebeam isocenter while irradiating the patient.

Various embodiments of the invention are described in this section toprovide specific details for a thorough understanding and enablingdescription of these embodiments. A person skilled in the art, however,will understand that the invention may be practiced without several ofthese details, or that additional details can be added to the invention.Where the context permits, singular or plural terms may also include theplural or singular term, respectively. Moreover, unless the word “or” isexpressly limited to mean only a single item exclusive from the otheritems in reference to a list of at least two items, then the use of “or”in such a list is to be interpreted as including (a) any single item inthe list, (b) all of the items in the list, or (c) any combination ofitems in the list. Additionally, the term “comprising” is usedthroughout to mean including at least the recited feature(s) such thatany greater number of the same feature and/or types of other features orcomponents are not precluded.

B. Radiation Therapy Systems with Real Time Tracking Systems

FIGS. 1 and 2 illustrate various aspects of a radiation therapy system 1for applying guided radiation therapy to a target 2 (e.g., a tumor)within a lung 4, prostate, breast, head, neck or other part of a patient6. The radiation therapy system 1 has a localization system 10 and aradiation delivery device 20. The localization system 10 is a trackingunit that locates and tracks the actual position of the target 2 in realtime during treatment planning, patient setup, and/or while applyingionizing radiation to the target from the radiation delivery device.Thus, although the target 2 may move within the patient because ofbreathing, organ filling/emptying, cardiac functions or other internalmovement as described above, the localization system 10 accuratelytracks the motion of the target relative to the external reference frameof the radiation delivery device or other external reference frameoutside of the patient to accurately deliver radiation within a smallmargin around the target. The localization system 10 can also monitorthe configuration and trajectory of the marker to provide an earlyindicator of a change in the tumor without using ionizing radiation.Moreover, the localization system 10 continuously tracks the target andprovides objective data (e.g., three-dimensional coordinates in anabsolute reference frame) to a memory device, user interface, linearaccelerator, and/or other device. The system 1 is described below in thecontext of guided radiation therapy for treating a tumor or other targetin the lung of the patient, but the system can be used for tracking andmonitoring the prostate gland or other targets within the patient forother therapeutic and/or diagnostic purposes.

The radiation delivery source of the illustrated embodiment is anionizing radiation device 20 (i.e., a linear accelerator). Suitablelinear accelerators are manufactured by Varian Medical Systems, Inc. ofPalo Alto, Calif.; Siemens Medical Systems, Inc. of Iselin, N.J.; ElektaInstruments, Inc. of Iselin, N.J.; or Mitsubishi Denki Kabushik Kaishaof Japan. Such linear accelerators can deliver conventional single ormulti-field radiation therapy, 3D conformal radiation therapy (3D CRT),intensity modulated radiation therapy (IMRT), stereotactic radiotherapy,and tomo therapy. The radiation delivery source 20 can deliver a gated,contoured or shaped beam 21 of ionizing radiation from a movable gantry22 to an area or volume at a known location in an external, absolutereference frame relative to the radiation delivery source 20. The pointor volume to which the ionizing radiation beam 21 is directed isreferred to as the machine isocenter.

The tracking system includes the localization system 10 and one or moremarkers 40. The localization system 10 determines the actual location ofthe markers 40 in a three-dimensional reference frame, and the markers40 are typically implanted within the patient 6. In the embodimentillustrated in FIGS. 1 and 2, more specifically, three markersidentified individually as markers 40 a-c are implanted in or near thelung 4 of the patient 6 at locations in or near the target 2. In otherapplications, a single marker, two markers, or more than three markerscan be used depending upon the particular application. Two markers, forexample, are desirable because the location of the target can bedetermined accurately, and also because any relative displacementbetween the two markers over time can be used to monitor markermigration in the patient. The markers 40 are desirably placed relativeto the target 2 such that the markers 40 are at least substantiallyfixed relative to the target 2 (e.g., the markers move directly with thetarget or at least in direct proportion to the movement of the target).The relative positions between the markers 40 and the relative positionsbetween a target isocenter T of the target 2 and the markers 40 can bedetermined with respect to an external reference frame defined by a CTscanner or other type of imaging system during a treatment planningstage before the patient is placed on the table. In the particularembodiment of the system 1 illustrated in FIGS. 1 and 2, thelocalization system 10 tracks the three-dimensional coordinates of themarkers 40 in real time relative to an absolute external reference frameduring the patient setup process and while irradiating the patient tomitigate collateral effects on adjacent healthy tissue and to ensurethat the desired dosage is applied to the target.

C. General Aspects of Markers and Localization Systems

FIG. 3 is a schematic view illustrating the operation of an embodimentof the localization system 10 and markers 40 a-c for treating a tumor orother target in the patient. The localization system 10 and the markers40 a-c are used to determine the location of the target 2 (FIGS. 1 and2) before, during and after radiation sessions. More specifically, thelocalization system 10 determines the locations of the markers 40 a-cand provides objective target position data to a memory, user interface,linear accelerator and/or other device in real time during setup,treatment, deployment, simulation, surgery, and/or other medicalprocedures. In one embodiment of the localization system, real timemeans that indicia of objective coordinates are provided to a userinterface at (a) a sufficiently high refresh rate (i.e., frequency) suchthat pauses in the data are not humanly discernable and (b) asufficiently low latency to be at least substantially contemporaneouswith the measurement of the location signal. In other embodiments, realtime is defined by higher frequency ranges and lower latency ranges forproviding the objective data to a radiation delivery device, or in stillother embodiments real time is defined as providing objective dataresponsive to the location of the markers (e.g., at a frequency thatadequately tracks the location of the target in real time and/or alatency that is substantially contemporaneous with obtaining positiondata of the markers).

1. Localization Systems

The localization system 10 includes an excitation source 60 (e.g., apulsed magnetic field generator), a sensor assembly 70, and a controller80 coupled to both the excitation source 60 and the sensor assembly 70.The excitation source 60 generates an excitation energy to energize atleast one of the markers 40 a-c in the patient 6 (FIG. 1). Theembodiment of the excitation source 60 shown in FIG. 3 produces a pulsedmagnetic field at different frequencies. For example, the excitationsource 60 can frequency multiplex the magnetic field at a firstfrequency E₁ to energize the first marker 40 a, a second frequency E₂ toenergize the second marker 40 b, and a third frequency E₃ to energizethe third marker 40 c. In response to the excitation energy, the markers40 a-c generate location signal L₁₋₃ at unique response frequencies.More specifically, the first marker 40 a generates a first locationsignal L₁ at a first frequency in response to the excitation energy atthe first frequency E₁, the second marker 40 b generates a secondlocation signal L₂ at a second frequency in response to the excitationenergy at the second frequency E₂, and the third marker 40 c generates athird location signal L₃ at a third frequency in response to theexcitation energy at the third frequency E₃. In an alternativeembodiment with two markers, the excitation source generates themagnetic field at frequencies E₁ and E₂, and the markets 40 a-b generatelocation signals L₁ and L₂, respectively.

The sensor assembly 70 can include a plurality of coils to sense thelocation signals L₁₋₃ from the markers 40 a-c. The sensor assembly 70can be a flat panel having a plurality of coils that are at leastsubstantially coplanar relative to each other. In other embodiments, thesensor assembly 70 may be a non-planar array of coils.

The controller 80 includes hardware, software or other computer-operablemedia containing instructions that operate the excitation source 60 tomultiplex the excitation energy at the different frequencies E₁₋₃. Forexample, the controller 80 causes the excitation source 60 to generatethe excitation energy at the first frequency E₁ for a first excitationperiod, and then the controller 80 causes the excitation source 60 toterminate the excitation energy at the first frequency E₁ for a firstsensing phase during which the sensor assembly 70 senses the firstlocation signal L₁ from the first marker 40 a without the presence ofthe excitation energy at the first frequency E₁. The controller 80 thencauses the excitation source 60 to: (a) generate the second excitationenergy at the second frequency E₂ for a second excitation period; and(b) terminate the excitation energy at the second frequency E₂ for asecond sensing phase during which the sensor assembly 70 senses thesecond location signal L₂ from the second marker 40 b without thepresence of the second excitation energy at the second frequency E₂. Thecontroller 80 then repeats this operation with the third excitationenergy at the third frequency E₃ such that the third marker 40 ctransmits the third location signal L₃ to the sensor assembly 70 duringa third sensing phase. As such, the excitation source 60 wirelesslytransmits the excitation energy in the form of pulsed magnetic fields atthe resonant frequencies of the markers 40 a-c during excitationperiods, and the markers 40 a-c wirelessly transmit the location signalsL₁₋₃ to the sensor assembly 70 during sensing phases. It will beappreciated that the excitation and sensing phases can be repeated topermit averaging of the sensed signals to reduce noise.

The computer-operable media in the controller 80, or in a separatesignal processor, or other computer also includes instructions todetermine the absolute positions of each of the markers 40 a-c in athree-dimensional reference frame. Based on signals provided by thesensor assembly 70 that correspond to the magnitude of each of thelocation signals L₁₋₃, the controller 80 and/or a separate signalprocessor calculates the absolute coordinates of each of the markers 40a-c in the three-dimensional reference frame. The absolute coordinatesof the markers 40 a-c are objective data that can be used to calculatethe coordinates of the target in the reference frame. When multiplemarkers are used, the rotation of the target can also be calculated.

2. Real Time Tracking

The localization system 10 and at least one of a marker 40 enables realtime tracking of the target 2 relative to the machine isocenter oranother external reference frame outside of the patient during treatmentplanning, set up, radiation sessions, and at other times of theradiation therapy process. In many embodiments, real time tracking meanscollecting position data of the markers, determining the locations ofthe markers in an external reference frame, and providing an objectiveoutput in the external reference frame that is responsive to thelocation of the markers. The objective output is provided at a frequencythat adequately tracks the target in real time and/or a latency that isat least substantially contemporaneous with collecting the position data(e.g., within a generally concurrent period of time).

For example, several embodiments of real time tracking are defined asdetermining the locations of the markers and calculating the location ofthe target relative to the machine isocenter at (a) a sufficiently highfrequency so that pauses in representations of the target location at auser interface do not interrupt the procedure or are readily discernableby a human, and (b) a sufficiently low latency to be at leastsubstantially contemporaneous with the measurement of the locationsignals from the markers. Alternatively, real time means that thelocation system 10 calculates the absolute position of each individualmarker 40 and/or the location of the target at a periodicity of 1 ms to5 seconds, or in many applications at a periodicity of approximately10-100 ms, or in some specific applications at a periodicity ofapproximately 20-50 ms. In applications for user interfaces, forexample, the periodicity can be 12.5 ms (i.e., a frequency of 80 Hz),16.667 ms (60 Hz), 20 ms (50 Hz), and/or 50 ms (20 Hz).

Alternatively, real time tracking can further mean that the locationsystem 10 provides the absolute locations of the markers 40 and/or thetarget 2 to a memory device, user interface, linear accelerator or otherdevice within a latency of 10 ms to 5 seconds from the time thelocalization signals were transmitted from the markers 40. In morespecific applications, the location system generally provides thelocations of the markers 40 and/or target 2 within a latency of about20-50 ms. The location system 10 accordingly provides real time trackingto monitor the position of the markers 40 and/or the target 2 withrespect to an external reference frame in a manner that is expected toenhance the efficacy of radiation therapy because higher radiation dosescan be applied to the target and collateral effects to healthy tissuecan be mitigated.

Alternatively, real-time tracking can further be defined by the trackingerror. Measurements of the position of a moving target are subject tomotion-induced error, generally referred to as a tracking error.According to aspects of the present invention, the localization system10 and at least one marker 4 enable real time tracking of the target 2relative to the machine isocenter or another external reference framewith a tracking error that is within clinically meaningful limits.

Tracking errors are due to two limitations exhibited by any practicalmeasurement system, specifically (a) latency between the time the targetposition is sensed and the time the position measurement is madeavailable, and (b) sampling delay due to the periodicity ofmeasurements. For example, if a target is moving at 5 cm/s and ameasurement system has a latency of 200 ms, then position measurementswill be in error by 1 cm. The error in this example is due to latencyalone, independent of any other measurement errors, and is simply due tothe fact that the target has moved between the time its position issensed and the time the position measurement is made available for use.If this exemplary measurement system further has a sampling periodicityof 200 ms (i.e., a sampling frequency of 5 Hz), then the peak trackingerror increases to 2 cm, with an average tracking error of 1.5 cm.

For a real time tracking system to be useful in medical applications, itis desirable to keep the tracking error within clinically meaningfullimits. For example, in a system for tracking motion of a tumor in alung for radiation therapy, it may be desirable to keep the trackingerror within 5 mm. Acceptable tracking errors may be smaller whentracking other organs for radiation therapy. In accordance with aspectsof the present invention, real time tracking refers to measurement oftarget position and/or rotation with tracking errors that are withinclinically meaningful limits.

The system described herein uses one or more markers to serve asregistration points to characterize target location, rotation, andmotion. In accordance with aspects of the invention, the markers have asubstantially fixed relationship with the target. If the markers did nothave a substantially fixed relationship with the target another type oftracking error would be incurred. This generally requires the markers tobe fixed or implanted sufficiently close to the target in order thattracking errors be within clinically meaningful limits, thus, themarkers may be placed in tissue or bone that exhibits representativemotion of the target. For example, with respect to the prostate, tissuethat is representative of the target's motion would include tissue inclose proximity or adjacent to the prostate. Tissue adjacent to a targetinvolving the prostate may include the prostate gland, the tumor itself,or tissue within a specified radial distance from the target. Withrespect to the prostate, tracking tissue that is a 5 cm radial distancefrom the target would provide representative motion that is clinicallyuseful to the motion of the target. In accordance with alternativetarget tracking locations, the radial distance may be greater or lesser.

According to aspects of the present invention, the marker motion is asurrogate for the motion of the target. Accordingly, the marker isplaced such that it moves in direct correlation to the target beingtracked. Depending on the target being tracked, the direct correlationrelationship between the target and the marker will vary. For example,in long bones, the marker may be place anywhere along the bone toprovide motion that directly correlations to target motion in the bone.With respect to soft tissue that moves substantially in response to thebony anatomy, for example, the head and neck, the marker may be placedin a bite block to provide surrogate motion in direct correlation withtarget motion. With respect to soft tissue and as discussed in detailabove, the target may be placed in adjacent soft tissue to provide asurrogate having direct correlation to target motion.

FIG. 4 is a flow diagram illustrating several aspects and uses of realtime tracking to monitor the location and the status of the target. Inthis embodiment, an integrated method 90 for radiation therapy includesa radiation planning procedure 91 that determines the plan for applyingthe radiation to the patient over a number of radiation fractions. Theradiation planning procedure 91 typically includes an imaging stage inwhich images of a tumor or other types of targets are obtained usingX-rays, CT, MRI, or ultrasound imaging. The images are analyzed by aperson to measure the relative distances between the markers and therelative position between the target and the markers. FIG. 5A, forexample, is a representation of a CT image showing a cross-section ofthe patient 6, the target 2, and a marker 40. Referring to FIG. 5B, thecoordinates (x₀, y₀, z₀) of the marker 40 in a reference frame R_(CT) ofthe CT scanner can be determined by an operator. The coordinates of thetumor can be determined in a similar manner to ascertain the offsetbetween the marker and the target.

The radiation planning procedure 91 can also include tracking thetargets using the localization system 10 (FIG. 3) in an observation areaseparate from the imaging equipment. The markers 40 (FIG. 3) can betracked to identify changes in the configuration (e.g., size/shape) ofthe target over time and to determine the trajectory of the targetcaused by movement of the target within the patient (e.g., simulation).For many treatment plans, the computer does not need to provideobjective output data of the marker or target locations to a user inreal time, but rather the data can be recorded in real time. Based onthe images obtained during the imaging stage and the additional dataobtained by tracking the markers using the localization system 10 in asimulation procedure, a treatment plan is developed for applying theradiation to the target.

The localization system 10 and the markers 40 enable an automatedpatient setup process for delivering the radiation. After developing atreatment plan, the method 90 includes a setup procedure 92 in which thepatient is positioned on a movable support table so that the target andmarkers are generally adjacent to the sensor assembly. As describedabove, the excitation source is activated to energize the markers, andthe sensors measure the strength of the signals from the markers. Thecomputer controller then (a) calculates objective values of thelocations of the markers and the target relative to the machineisocenter, and (b) determines an objective offset value between theposition of the target and the machine isocenter. Referring to FIG. 6,for example, the objective offset values can be provided to a userinterface that displays the vertical, lateral and longitudinal offsetsof the target relative to the machine isocenter. A user interface may,additionally or instead, display target rotation.

One aspect of several embodiments of the localization system 10 is thatthe objective values are provided to the user interface or other deviceby processing the position data from the field sensor 70 in thecontroller 80 or other computer without human interpretation of the datareceived by the field sensor 70. If the offset value is outside of anacceptable range, the computer automatically activates the controlsystem of the support table to move the tabletop relative to the machineisocenter until the target isocenter is coincident with the machineisocenter. The computer controller generally provides the objectiveoutput data of the offset to the table control system in real time asdefined above. For example, because the output is provided to theradiation delivery device, it can be at a high rate (1-20 ms) and a lowlatency (10-20 ms). If the output data is provided to a user interfacein addition to or in lieu of the table controller, it can be at arelatively lower rate (20-50 ms) and higher latency (50-200 ms).

In one embodiment, the computer controller also determines the positionand orientation of the markers relative to the position and orientationof simulated markers. The locations of the simulated markers areselected so that the target will be at the machine isocenter when thereal markers are at the selected locations for the simulated markers. Ifthe markers are not properly aligned and oriented with the simulatedmarkers, the support table is adjusted as needed for proper markeralignment. This marker alignment properly positions the target along sixdimensions, namely X, Y, Z, pitch, yaw, and roll. Accordingly, thepatient is automatically positioned in the correct position and rotationrelative to the machine isocenter for precise delivery of radiationtherapy to the target.

Referring back to FIG. 4, the method 90 further includes a radiationsession 93. FIG. 7 shows a further aspect of an automated process inwhich the localization system 10 tracks the target during the radiationsession 93 and controls the radiation delivery device 20 according tothe offset between target and the machine isocenter. For example, if theposition of the target is outside of a permitted degree or range ofdisplacement from the machine isocenter, the localization system 10sends a signal to interrupt the delivery of the radiation or preventinitial activation of the beam. In another embodiment, the localizationsystem 10 sends signals to automatically reposition a tabletop 27 andthe patient 6 (as a unit) so that the target isocenter remains within adesired range of the machine isocenter during the radiation session 93even if the target moves. In still another embodiment, the localizationsystem 10 sends signals to activate the radiation only when the targetis within a desired range of the machine isocenter (e.g., gatedtherapy). In the case of treating a target in the lung, one embodimentof gated therapy includes tracking the target duringinspiration/expiration, having the patient hold his/her breath at theend of an inspiration/expiration cycle, and activating the beam 21 whenthe computer 80 determines that the objective offset value between thetarget and the machine isocenter is within a desired range. Accordingly,the localization system enables dynamic adjustment of the table 27and/or the beam 21 in real time while irradiating the patient. This isexpected to ensure that the radiation is accurately delivered to thetarget without requiring a large margin around the target.

The localization system provides the objective data of the offset and/orrotation to the linear accelerator and/or the patient support table inreal time as defined above. For example, as explained above with respectto automatically positioning the patent support table during the setupprocedure 92, the localization system generally provides the objectiveoutput to the radiation delivery device at least substantiallycontemporaneously with obtaining the position data of the markers and/orat a sufficient frequency to track the target in real time. Theobjective output, for example, can be provided at a short periodicity(1-20 ms) and a low latency (10-20 ms) such that signals for controllingthe beam 21 can be sent to the radiation delivery device 20 in the sametime periods during a radiation session. In another example of real timetracking, the objective output is provided a plurality of times duringan “on-beam” period (e.g., 2, 5, 10 or more times while the beam is on).In the case of terminating or activating the radiation beam, oradjusting the leafs of a beam collimator, it is generally desirable tomaximize the refresh rate and minimize the latency. In some embodiments,therefore, the localization system may provide the objective output dataof the target location and/or the marker locations at a periodicity of10 ms or less and a latency of 10 ms or less.

The method 90 further includes a verification procedure 94 in which thereal time objective output data from the radiation session 93 iscompared to the status of the parameters of the radiation beam. Forexample, the target locations can be correlated with the beam intensity,beam position, and collimator configuration at corresponding timeintervals during the radiation session 93. This correlation can be usedto determine the dose of radiation delivered to discrete regions in andaround the target. This information can also be used to determine theeffects of radiation on certain areas of the target by noting changes inthe target configuration or the target trajectory.

The method 90 can further include a first decision (Block 95) in whichthe data from the verification procedure 94 is analyzed to determinewhether the treatment is complete. If the treatment is not complete, themethod 90 further includes a second decision (Block 96) in which theresults of the verification procedure are analyzed to determine whetherthe treatment plan should be revised to compensate for changes in thetarget. If revisions are necessary, the method can proceed withrepeating the planning procedure 91. On the other hand, if the treatmentplan is providing adequate results, the method 90 can proceed byrepeating the setup procedure 92, radiation session 93, and verificationprocedure 94 in a subsequent fraction of the radiation therapy.

The localization system 10 provides several features, eitherindividually or in combination with each other, that enhance the abilityto accurately deliver high doses of radiation to targets within tightmargins. For example, many embodiments of the localization system useleadless markers that are implanted in the patient so that they aresubstantially fixed with respect to the target. The markers accordinglymove either directly with the target or in a relationship proportionalto the movement of the target. As a result, internal movement of thetarget caused by respiration, organ filling, cardiac functions, or otherfactors can be identified and accurately tracked before, during andafter medical procedures. Moreover, many aspects of the localizationsystem 10 use a non-ionizing energy to track the leadless markers in anexternal, absolute reference frame in a manner that provides objectiveoutput. In general, the objective output is determined in a computersystem without having a human interpret data (e.g., images) while thelocalization system 10 tracks the target and provides the objectiveoutput. This significantly reduces the latency between the time when theposition of the marker is sensed and the objective output is provided toa device or a user. For example, this enables an objective outputresponsive to the location of the target to be provided at leastsubstantially contemporaneously with collecting the position data of themarker. The system also effectively eliminates inter-user variabilityassociated with subjective interpretation of data (e.g., images).

D. Specific Embodiments of Markers and Localization Systems

The following specific embodiments of markers, excitation sources,sensors and controllers provide additional details to implement thesystems and processes described above with reference to FIGS. 1-7. Thepresent inventors overcame many challenges to develop markers andlocalization systems that accurately determine the location of a markerwhich (a) produces a wirelessly transmitted location signal in responseto a wirelessly transmitted excitation energy, and (b) has across-section small enough to be implanted in the lung, prostate, orother part of a patient. Systems with these characteristics have severalpractical advantages, including (a) not requiring ionization radiation,(b) not requiring line-of-sight between the markers and sensors, and (c)effecting an objective measurement of a target's location and/orrotation. The following specific embodiments are described in sufficientdetail to enable a person skilled in the art to make and use such alocalization system for radiation therapy involving a tumor in thepatient, but the invention is not limited to the following embodimentsof markers, excitation sources, sensor assemblies and/or controllers.

1. Markers

FIG. 8A is an isometric view of a marker 100 for use with thelocalization system 10 (FIGS. 1-7). The embodiment of the marker 100shown in FIG. 8A includes a casing 110 and a magnetic transponder 120(e.g., a resonating circuit) in the casing 110. The casing 110 is abarrier configured to be implanted in the patient, or encased within thebody of an instrument. The casing 110 can alternatively be configured tobe adhered externally to the skin of the patient. The casing 110 can bea generally cylindrical capsule that is sized to fit within the bore ofa small introducer, such as bronchoscope or percutaneous trans-thoracicimplanter, but the casing 110 can have other configurations and belarger or smaller. The casing 110, for example, can have barbs or otherfeatures to anchor the casing 110 in soft tissue or an adhesive forattaching the casing 110 externally to the skin of a patient. Suitableanchoring mechanisms for securing the marker 100 to a patient aredisclosed in International Publication No. WO 02/39917 A1, whichdesignates the United States and is incorporated herein by reference. Inone embodiment, the casing 110 includes (a) a capsule or shell 112having a closed end 114 and an open end 116, and (b) a sealant 118 inthe open end 116 of the shell 112. The casing 110 and the sealant 118can be made from plastics, ceramics, glass or other suitablebiocompatible materials.

The magnetic transponder 120 can include a resonating circuit thatwirelessly transmits a location signal in response to a wirelesslytransmitted excitation field as described above. In this embodiment, themagnetic transponder 120 comprises a coil 122 defined by a plurality ofwindings of a conductor 124. Many embodiments of the magnetictransponder 120 also include a capacitor 126 coupled to the coil 122.The coil 122 resonates at a selected resonant frequency. The coil 122can resonate at a resonant frequency solely using the parasiticcapacitance of the windings without having a capacitor, or the resonantfrequency can be produced using the combination of the coil 122 and thecapacitor 126. The coil 122 accordingly generates an alternatingmagnetic field at the selected resonant frequency in response to theexcitation energy either by itself or in combination with the capacitor126. The conductor 124 of the illustrated embodiment can be hot air oralcohol bonded wire having a gauge of approximately 45-52. The coil 122can have 800-1000 turns, and the windings are preferably wound in atightly layered coil. The magnetic transponder 120 can further include acore 128 composed of a material having a suitable magnetic permeability.For example, the core 128 can be a ferromagnetic element composed offerrite or another material. The magnetic transponder 120 can be securedto the casing 110 by an adhesive 129.

The marker 100 also includes an imaging element that enhances theradiographic image of the marker to make the marker more discernible inradiographic images. The imaging element also has a radiographic profilein a radiographic image such that the marker has a radiographic centroidat least approximately coincident with the magnetic centroid of themagnetic transponder 120. As explained in more detail below, theradiographic and magnetic centroids do not need to be exactly coincidentwith each other, but rather can be within an acceptable range.

FIG. 8B is a cross-sectional view of the marker 100 along line 8B-8B ofFIG. 8A that illustrates an imaging element 130 in accordance with anembodiment of the invention. The imaging element 130 illustrated inFIGS. 8A-B includes a first contrast element 132 and second contrastelement 134. The first and second contrast elements 132 and 134 aregenerally configured with respect to the magnetic transponder 120 sothat the marker 100 has a radiographic centroid R_(c) that is at leastsubstantially coincident with the magnetic centroid M_(c) of themagnetic transponder 120. For example, when the imaging element 130includes two contrast elements, the contrast elements can be arrangedsymmetrically with respect to the magnetic transponder 120 and/or eachother. The contrast elements can also be radiographically distinct fromthe magnetic transponder 120. In such an embodiment, the symmetricalarrangement of distinct contrast elements enhances the ability toaccurately determine the radiographic centroid of the marker 100 in aradiographic image.

The first and second contrast elements 132 and 134 illustrated in FIGS.8A-B are continuous rings positioned at opposing ends of the core 128.The first contrast element 132 can be at or around a first end 136 a ofthe core 128, and the second contrast element 134 can be at or around asecond end 136 b of the core 128. The continuous rings shown in FIGS.8A-B have substantially the same diameter and thickness. The first andsecond contrast elements 132 and 134, however, can have otherconfigurations and/or be in other locations relative to the core 128 inother embodiments. For example, the first and second contrast elements132 and 134 can be rings with different diameters and/or thicknesses.

The radiographic centroid of the image produced by the imaging element130 does not need to be absolutely coincident with the magnetic centroidM_(c), but rather the radiographic centroid and the magnetic centroidshould be within an acceptable range. For example, the radiographiccentroid R_(c) can be considered to be at least approximately coincidentwith the magnetic centroid M_(c) when the offset between the centroidsis less than approximately 5 mm. In more stringent applications, themagnetic centroid M_(c) and the radiographic centroid R_(c) areconsidered to be at least substantially coincident with each other whenthe offset between the centroids is 2 mm, or less than 1 mm. In otherapplications, the magnetic centroid M_(c) is at least approximatelycoincident with the radiographic centroid R_(c) when the centroids arespaced apart by a distance not greater than half the length of themagnetic transponder 120 and/or the marker 100.

The imaging element 130 can be made from a material and configuredappropriately to absorb a high fraction of incident photons of aradiation beam used for producing the radiographic image. For example,when the imaging radiation has high acceleration voltages in themegavoltage range, the imaging element 130 is made from, at least inpart, high density materials with sufficient thickness andcross-sectional area to absorb enough of the photon fluence incident onthe imaging element to be visible in the resulting radiograph. Many highenergy beams used for therapy have acceleration voltages of 6 MV-25 MV,and these beams are often used to produce radiographic images in the 5MV-10 MV range, or more specifically in the 6 MV-8 MV range. As such,the imaging element 130 can be made from a material that is sufficientlyabsorbent of incident photon fluence to be visible in an image producedusing a beam with an acceleration voltage of 5 MV-10 MV, or morespecifically an acceleration voltage of 6 MV-8 MV.

Several specific embodiments of imaging elements 130 can be made fromgold, tungsten, platinum and/or other high density metals. In theseembodiments the imaging element 130 can be composed of materials havinga density of 19.25 g/cm3 (density of tungsten) and/or a density ofapproximately 21.4 g/cm3 (density of platinum). Many embodiments of theimaging element 130 accordingly have a density not less than 19 g/cm3.In other embodiments, however, the material(s) of the imaging element130 can have a substantially lower density. For example, imagingelements with lower density materials are suitable for applications thatuse lower energy radiation to produce radiographic images. Moreover, thefirst and second contrast elements 132 and 134 can be composed ofdifferent materials such that the first contrast element 132 can be madefrom a first material and the second contrast element 134 can be madefrom a second material.

Referring to FIG. 8B, the marker 100 can further include a module 140 atan opposite end of the core 128 from the capacitor 126. In theembodiment of the marker 100 shown in FIG. 8B, the module 140 isconfigured to be symmetrical with respect to the capacitor 126 toenhance the symmetry of the radiographic image. As with the first andsecond contrast elements 132 and 134, the module 140 and the capacitor126 are arranged such that the magnetic centroid of the marker is atleast approximately coincident with the radiographic centroid of themarker 100. The module 140 can be another capacitor that is identical tothe capacitor 126, or the module 140 can be an electrically inactiveelement. Suitable electrically inactive modules include ceramic blocksshaped like the capacitor 126 and located with respect to the coil 122,the core 128 and the imaging element 130 to be symmetrical with eachother. In still other embodiments the module 140 can be a different typeof electrically active element electrically coupled to the magnetictransponder 120.

One specific process of using the marker involves imaging the markerusing a first modality and then tracking the target of the patientand/or the marker using a second modality. For example, the location ofthe marker relative to the target can be determined by imaging themarker and the target using radiation. The marker and/or the target canthen be localized and tracked using the magnetic field generated by themarker in response to an excitation energy.

The marker 100 shown in FIGS. 8A-B is expected to provide an enhancedradiographic image compared to conventional magnetic markers for moreaccurately determining the relative position between the marker and thetarget of a patient. FIG. 8C, for example, illustrates a radiographicimage 150 of the marker 100 and a target T of the patient. The first andsecond contrast elements 132 and 134 are expected to be more distinct inthe radiographic image 150 because they can be composed of higherdensity materials than the components of the magnetic transponder 120.The first and second contrast elements 132 and 134 can accordinglyappear as bulbous ends of a dumbbell shape in applications in which thecomponents of the magnetic transponder 120 are visible in the image. Incertain megavolt applications, the components of the magnetictransponder 120 may not appear at all on the radiographic image 150 suchthat the first and second contrast elements 132 and 134 will appear asdistinct regions that are separate from each other. In eitherembodiment, the first and second contrast elements 132 and 134 provide areference frame in which the radiographic centroid R_(c) of the marker100 can be located in the image 150. Moreover, because the imagingelement 130 is configured so that the radiographic centroid R_(c) is atleast approximately coincident with the magnetic centroid M_(c), therelative offset or position between the target T and the magneticcentroid M_(c) can be accurately determined using the marker 100. Theembodiment of the marker 100 illustrated in FIGS. 8A-C, therefore, isexpected to mitigate errors caused by incorrectly estimating theradiographic and magnetic centroids of markers in radiographic images.

FIG. 9A is an isometric view of a marker 200 with a cut-away portion toillustrate internal components, and FIG. 9B is a cross-sectional view ofthe marker 200 taken along line 9B-9B of FIG. 9A. The marker 200 issimilar to the marker 100 shown above in FIG. 8A, and thus likereference numbers refer to like components. The marker 200 differs fromthe marker 100 in that the marker 200 includes an imaging element 230defined by a single contrast element. The imaging element 230 isgenerally configured relative to the magnetic transponder 120 so thatthe radiographic centroid of the marker 200 is at least approximatelycoincident with the magnetic centroid of the magnetic transponder 120.The imaging element 230, more specifically, is a ring extending aroundthe coil 122 at a medial region of the magnetic transponder 120. Theimaging element 230 can be composed of the same materials describedabove with respect to the imaging element 130 in FIGS. 8A-B. The imagingelement 230 can have an inner diameter that is approximately equal tothe outer diameter of the coil 122, and an outer diameter within thecasing 110. As shown in FIG. 9B, however, a spacer 231 can be betweenthe inner diameter of the imaging element 230 and the outer diameter ofthe coil 122.

The marker 200 is expected to operate in a manner similar to the marker100 described above. The marker 200, however, does not have two separatecontrast elements that provide two distinct, separate points in aradiographic image. The imaging element 230 is still highly useful inthat it identifies the radiographic centroid of the marker 200 in aradiographic image, and it can be configured so that the radiographiccentroid of the marker 200 is at least approximately coincident with themagnetic centroid of the magnetic transponder 120.

FIG. 10A is an isometric view of a marker 300 having a cut-away portion,and FIG. 10B is a cross-sectional view of the marker 300 taken alongline 10B-10B of FIG. 10A. The marker 300 is substantially similar to themarker 200 shown in FIGS. 9A-B, and thus like reference numbers refer tolike components in FIGS. 8A-10B. The imaging element 330 can be a highdensity ring configured relative to the magnetic transponder 120 so thatthe radiographic centroid of the marker 300 is at least approximatelycoincident with the magnetic centroid of the magnetic transponder 120.The marker 300, more specifically, includes an imaging element 330around the casing 110. The marker 300 is expected to operate in much thesame manner as the marker 200 shown in FIGS. 9A-B.

FIG. 11 is an isometric view with a cut-away portion illustrating amarker 400 in accordance with another embodiment of the invention. Themarker 400 is similar to the marker 100 shown in FIGS. 8A-C, and thuslike reference numbers refer to like components in these Figures. Themarker 400 has an imaging element 430 including a first contrast element432 at one end of the magnetic transponder 120 and a second contrastelement 434 at another end of the magnetic transponder 120. The firstand second contrast elements 432 and 434 are spheres composed ofsuitable high density materials. The contrast elements 432 and 434, forexample, can be composed of gold, tungsten, platinum or other suitablehigh-density materials for use in radiographic imaging. The marker 400is expected to operate in a manner similar to the marker 100, asdescribed above.

FIG. 12 is an isometric view with a cut-away portion of a marker 500 inaccordance with yet another embodiment of the invention. The marker 500is substantially similar to the markers 100 and 400 shown in FIGS. 8Aand 11, and thus like reference numbers refer to like components inthese Figures. The marker 500 includes an imaging element 530 includinga first contrast element 532 and a second contrast element 534. Thefirst and second contrast elements 532 and 534 can be positionedproximate to opposing ends of the magnetic transponder 120. The firstand second contrast elements 532 and 534 can be discontinuous ringshaving a gap 535 to mitigate eddy currents. The contrast elements 532and 534 can be composed of the same materials as described above withrespect to the contrast elements of other imaging elements in accordancewith other embodiments of the invention.

Additional embodiments of markers in accordance with the invention caninclude imaging elements incorporated into or otherwise integrated withthe casing 110, the core 128 (FIG. 8B) of the magnetic transponder 120,and/or the adhesive 129 (FIG. 8B) in the casing. For example, particlesof a high density material can be mixed with ferrite and extruded toform the core 128. Alternative embodiments can mix particles of a highdensity material with glass or another material to form the casing 110,or coat the casing 110 with a high-density material. In still otherembodiments, a high density material can be mixed with the adhesive 129and injected into the casing 110. Any of these embodiments canincorporate the high density material into a combination of the casing110, the core 128 and/or the adhesive 129. Suitable high densitymaterials can include tungsten, gold and/or platinum as described above.

The markers described above with reference to FIGS. 8A-12 can be usedfor the markers 40 in the localization system 10 (FIGS. 1-7). Thelocalization system 10 can have several markers with the same type ofimaging elements, or markers with different imaging elements can be usedwith the same instrument. Several additional details of these markersand other embodiments of markers are described in U.S. application Ser.Nos. 10/334,698 and 10/746,888, which are incorporated herein byreference. For example, the markers may not have any imaging elementsfor applications with lower energy radiation, or the markers may havereduced volumes of ferrite and metals to mitigate issues with MRIimaging as set forth in U.S. application Ser. No. 10/334,698.

2. Localization Systems

FIG. 13 is a schematic block diagram of a localization system 1000 fordetermining the absolute location of the markers 40 (shownschematically) relative to a reference frame. The localization system1000 includes an excitation source 1010, a sensor assembly 1012, asignal processor 1014 operatively coupled to the sensor assembly 1012,and a controller 1016 operatively coupled to the excitation source 1010and the signal processor 1014. The excitation source 1010 is oneembodiment of the excitation source 60 described above with reference toFIG. 3; the sensor assembly 1012 is one embodiment of the sensorassembly 70 described above with reference to FIG. 3; and the controller1016 is one embodiment of the controller 80 described above withreference to FIG. 3.

The excitation source 1010 is adjustable to generate a magnetic fieldhaving a waveform with energy at selected frequencies to match theresonant frequencies of the markers 40. The magnetic field generated bythe excitation source 1010 energizes the markers at their respectivefrequencies. After the markers 40 have been energized, the excitationsource 1010 is momentarily switched to an “off” position so that thepulsed magnetic excitation field is terminated while the markerswirelessly transmit the location signals. This allows the sensorassembly 1012 to sense the location signals from the markers 40 withoutmeasurable interference from the significantly more powerful magneticfield from the excitation source 1010. The excitation source 1010accordingly allows the sensor assembly 1012 to measure the locationsignals from the markers 40 at a sufficient signal-to-noise ratio sothat the signal processor 1014 or the controller 1016 can accuratelycalculate the absolute location of the markers 40 relative to areference frame.

a. Excitation Sources

Referring still to FIG. 13, the excitation source 1010 includes a highvoltage power supply 1040, an energy storage device 1042 coupled to thepower supply 1040, and a switching network 1044 coupled to the energystorage device 1042. The excitation source 1010 also includes a coilassembly 1046 coupled to the switching network 1044. In one embodiment,the power supply 1040 is a 500 volt power supply, although other powersupplies with higher or lower voltages can be used. The energy storagedevice 1042 in one embodiment is a high voltage capacitor that can becharged and maintained at a relatively constant charge by the powersupply 1040. The energy storage device 1042 alternately provides energyto and receives energy from the coils in the coil assembly 1046.

The energy storage device 1042 is capable of storing adequate energy toreduce voltage drop in the energy storage device while having a lowseries resistance to reduce power losses. The energy storage device 1042also has a low series inductance to more effectively drive the coilassembly 1046. Suitable capacitors for the energy storage device 1042include aluminum electrolytic capacitors used in flash energyapplications. Alternative energy storage devices can also include NiCdand lead acid batteries, as well as alternative capacitor types, such astantalum, film, or the like.

The switching network 1044 includes individual H-bridge switches 1050(identified individually by reference numbers 1050 a-d), and the coilassembly 1046 includes individual source coils 1052 (identifiedindividually by reference numbers 1052 a-d). Each H-bridge switch 1050controls the energy flow between the energy storage device 1042 and oneof the source coils 1052. For example, H-bridge switch #1 1050 aindependently controls the flow of the energy to/from source coil #11052 a, H-bridge switch #2 1050 b independently controls the flow of theenergy to/from source coil #2 1052 b, H-bridge switch #3 1050 cindependently controls the flow of the energy to/from source coil #31052 c, and H-bridge switch #4 1050 d independently controls the flow ofthe energy to/from source coil #4 1052 d. The switching network 1044accordingly controls the phase of the magnetic field generated by eachof the source coils 1052 a-d independently. The H-bridges 1050 can beconfigured so that the electrical signals for all the source coils 1052are in phase, or the H-bridge switches 1050 can be configured so thatone or more of the source coils 1052 are 180° out of phase. Furthermore,the H-bridge switches 1050 can be configured so that the electricalsignals for one or more of the source coils 1052 are between 0 and 180°out of phase to simultaneously provide magnetic fields with differentphases.

The source coils 1052 can be arranged in a coplanar array that is fixedrelative to the reference frame. Each source coil 1052 can be a square,planar winding arranged to form a flat, substantially rectilinear coil.The source coils 1052 can have other shapes and other configurations indifferent embodiments. In one embodiment, the source coils 1052 areindividual conductive lines formed in a stratum of a printed circuitboard, or windings of a wire in a foam frame. Alternatively, the sourcecoils 1052 can be formed in different substrates or arranged so that twoor more of the source coils are not planar with each other.Additionally, alternate embodiments of the invention may have fewer ormore source coils than illustrated in FIG. 13.

The selected magnetic fields from the source coils 1052 combine to forman adjustable excitation field that can have different three-dimensionalshapes to excite the markers 40 at any spatial orientation within anexcitation volume. When the planar array of the source coils 1052 isgenerally horizontal, the excitation volume is positioned above an areaapproximately corresponding to the central region of the coil assembly1046. The excitation volume is the three-dimensional space adjacent tothe coil assembly 1046 in which the strength of the magnetic field issufficient to adequately energize the markers 40.

FIGS. 14-16 are schematic views of a planar array of the source coils1052 with the alternating electrical signals provided to the sourcecoils in different combinations of phases to generate excitation fieldsabout different axes relative to the illustrated XYZ coordinate system.Each source coil 1052 has two outer sides 1112 and two inner sides 1114.Each inner side 1114 of one source coil 1052 is immediately adjacent toan inner side 1114 of another source coil 1052, but the outer sides 1112of all the source coils 1052 are not adjacent to any other source coil1052.

In the embodiment of FIG. 14, all the source coils 1052 a-dsimultaneously receive an alternating electrical signals in the samephase. As a result, the electrical current flows in the same directionthrough all the source coils 1052 a-d such that a direction 1113 of thecurrent flowing along the inner sides 1114 of one source coil (e.g.,source coil 1052 a) is opposite to the direction 1113 of the currentflowing along the inner sides 1114 of the two adjacent source coils(e.g., source coils 1052 c and 1052 d). The magnetic fields generatedalong the inner sides 1114 accordingly cancel each other out so that themagnetic field is effectively generated from the current flowing alongthe outer sides 1112 of the source coils. The resulting excitation fieldformed by the combination of the magnetic fields from the source coils1052 a-d shown in FIG. 14 has a magnetic moment 1115 generally in the Zdirection within an excitation volume 1109. This excitation fieldenergizes markers parallel to the Z-axis or markers positioned with anangular component along the Z-axis (i.e., not orthogonal to the Z-axis).

FIG. 15 is a schematic view of the source coils 1052 a-d with thealternating electrical signals provided in a second combination ofphases to generate a second excitation field with a different spatialorientation. In this embodiment, source coils 1052 a and 1052 c are inphase with each other, and source coils 1052 b and 1052 d are in phasewith each other. However, source coils 1052 a and 1052 c are 180 degreesout of phase with source coils 1052 b and 1052 d. The magnetic fieldsfrom the source coils 1052 a-d combine to generate an excitation fieldhaving a magnetic moment 1217 generally in the Y direction within theexcitation volume 1109. Accordingly, this excitation field energizesmarkers parallel to the Y-axis or markers positioned with an angularcomponent along the Y-axis.

FIG. 16 is a schematic view of the source coils 1052 a-d with thealternating electrical signals provided in a third combination of phasesto generate a third excitation field with a different spatialorientation. In this embodiment, source coils 1052 a and 1052 b are inphase with each other, and source coils 1052 c and 1052 d are in phasewith each other. However, source coils 1052 a and 1052 b are 180 degreesout of phase with source coils 1052 c and 1052 d. The magnetic fieldsfrom the source coils 1052 a-d combine to generate an excitation fieldhaving a magnetic moment 1319 in the excitation volume 1109 generally inthe direction of the X-axis. Accordingly, this excitation fieldenergizes markers parallel to the X-axis or markers positioned with anangular component along the X-axis.

FIG. 17 is a schematic view of the source coils 1052 a-d illustratingthe current flow to generate an excitation field 1424 for energizingmarkers 40 with longitudinal axes parallel to the Y-axis. The switchingnetwork 1044 (FIG. 13) is configured so that the phases of thealternating electrical signals provided to the source coils 1052 a-d aresimilar to the configuration of FIG. 15. This generates the excitationfield 1424 with a magnetic moment in the Y direction to energize themarkers 40.

FIG. 18 further illustrates the ability to spatially adjust theexcitation field in a manner that energizes any of the markers 40 atdifferent spatial orientations. In this embodiment, the switchingnetwork 1044 (FIG. 13) is configured so that the phases of thealternating electrical signals provided to the source coils 1052 a-d aresimilar to the configuration shown in FIG. 14. This produces anexcitation field with a magnetic moment in the Z direction thatenergizes markers 40 with longitudinal axes parallel to the Z-axis.

The spatial configuration of the excitation field in the excitationvolume 1109 can be quickly adjusted by manipulating the switchingnetwork to change the phases of the electrical signals provided to thesource coils 1052 a-d. As a result, the overall magnetic excitationfield can be changed to be oriented in either the X, Y or Z directionswithin the excitation volume 1109. This adjustment of the spatialorientation of the excitation field reduces or eliminates blind spots inthe excitation volume 1109. Therefore, the markers 40 within theexcitation volume 1109 can be energized by the source coils 1052 a-dregardless of the spatial orientations of the leadless markers.

In one embodiment, the excitation source 1010 is coupled to the sensorassembly 1012 so that the switching network 1044 (FIG. 13) adjustsorientation of the pulsed generation of the excitation field along theX, Y, and Z axes depending upon the strength of the signal received bythe sensor assembly. If the location signal from a marker 40 isinsufficient, the switching network 1044 can automatically change thespatial orientation of the excitation field during a subsequent pulsingof the source coils 1052 a-d to generate an excitation field with amoment in the direction of a different axis or between axes. Theswitching network 1044 can be manipulated until the sensor assembly 1012receives a sufficient location signal from the marker.

The excitation source 1010 illustrated in FIG. 13 alternately energizesthe source coils 1052 a-d during an excitation phase to power themarkers 40, and then actively de-energizes the source coils 1052 a-dduring a sensing phase in which the sensor assembly 1012 senses thedecaying location signals wirelessly transmitted by the markers 40. Toactively energize and de-energize the source coils 1052 a-d, theswitching network 1044 is configured to alternatively transfer storedenergy from the energy storage device 1042 to the source coils 1052 a-d,and to then re-transfer energy from the source coils 1052 a-d back tothe energy storage device 1042. The switching network 1044 alternatesbetween first and second “on” positions so that the voltage across thesource coils 1052 alternates between positive and negative polarities.For example, when the switching network 1044 is switched to the first“on” position, the energy in the energy storage device 1042 flows to thesource coils 1052 a-d. When the switching network 1044 is switched tothe second “on” position, the polarity is reversed such that the energyin the source coils 1052 a-d is actively drawn from the source coils1052 a-d and directed back to the energy storage device 1042. As aresult, the energy in the source coils 1052 a-d is quickly transferredback to the energy storage device 1042 to abruptly terminate theexcitation field transmitted from the source coils 1052 a-d and toconserve power consumed by the energy storage device 1042. This removesthe excitation energy from the environment so that the sensor assembly1012 can sense the location signals from the markers 40 withoutinterference from the significantly larger excitation energy from theexcitation source 1010. Several additional details of the excitationsource 1010 and alternate embodiments are disclosed in U.S. patentapplication Ser. No. 10/213,980 filed on Aug. 7, 2002, and now U.S. Pat.No. 6,822,570, which is incorporated by reference herein in itsentirety.

b. Sensor Assemblies

FIG. 19A is an exploded isometric view showing several components of thesensor assembly 1012 for use in the localization system 1000 (FIG. 13).The sensor assembly 1012 includes a sensing unit 1601 having a pluralityof coils 1602 formed on or carried by a panel 1604. The coils 1602 canbe field sensors or magnetic flux sensors arranged in a sensor array1605.

The panel 1604 may be a substantially non-conductive material, such as asheet of KAPTON® produced by DuPont. KAPTON® is particularly useful whenan extremely stable, tough, and thin film is required (such as to avoidradiation beam contamination), but the panel 1604 may be made from othermaterials and have other configurations. For example, FR4 (epoxy-glasssubstrates), GETEK or other Teflon-based substrates, and othercommercially available materials can be used for the panel 1604.Additionally, although the panel 1604 may be a flat, highly planarstructure, in other embodiments, the panel may be curved along at leastone axis. In either embodiment, the field sensors (e.g., coils) arearranged in a locally planar array in which the plane of one fieldsensor is at least substantially coplanar with the planes of adjacentfield sensors. For example, the angle between the plane defined by onecoil relative to the planes defined by adjacent coils can be fromapproximately 0° to 10°, and more generally is less than 5°. In somecircumstances, however, one or more of the coils may be at an anglegreater than 10° relative to other coils in the array.

The sensor assembly 1012 shown in FIG. 19A can optionally include a core1620 laminated to the panel 1604. The core 1620 can be a support membermade from a rigid material, or the core 1620 can be a low density foam,such as a closed-cell Rohacell foam. The core 1620 is preferably astable layer that has a low coefficient of thermal expansion so that theshape of the sensor assembly 1012 and the relative orientation betweenthe coils 1602 remain within a defined range over an operatingtemperature range.

The sensor assembly 1012 can further include a first exterior cover 1630a on one side of the sensing subsystem and a second exterior cover 1630b on an opposing side. The first and second exterior covers 1630 a-b canbe thin, thermally stable layers, such as Kevlar or Thermount films.Each of the first and second exterior covers 1630 a-b can includeelectric shielding 1632 to block undesirable external electric fieldsfrom reaching the coils 1602. The electric shielding 1632 can be aplurality of parallel legs of gold-plated, copper strips to define acomb-shaped shield in a configuration commonly called a Faraday shield.It will be appreciated that the shielding can be formed from othermaterials that are suitable for shielding. The electric shielding can beformed on the first and second exterior covers using printed circuitboard manufacturing technology or other techniques.

The panel 1604 with the coils 1602 is laminated to the core 1620 using apressure sensitive adhesive or another type of adhesive. The first andsecond exterior covers 1630 a-b are similarly laminated to the assemblyof the panel 1604 and the core 1620. The laminated assembly forms arigid structure that fixedly retains the arrangement of the coils 1602in a defined configuration over a large operating temperature range. Assuch, the sensor assembly 1012 does not substantially deflect across itssurface during operation. The sensor assembly 1012, for example, canretain the array of coils 1602 in the fixed position with a deflectionof no greater than ±0.5 mm, and in some cases no more than ±0.3 mm. Thestiffness of the sensing subsystem provides very accurate and repeatablemonitoring of the precise location of leadless markers in real time.

In still another embodiment, the sensor assembly 1012 can furtherinclude a plurality of source coils that are a component of theexcitation source 1010. One suitable array combining the sensor assembly1012 with source coils is disclosed in U.S. patent application Ser. No.10/334,700, entitled PANEL-TYPE SENSOR/SOURCE ARRAY ASSEMBLY, filed onDec. 30, 2002, which is herein incorporated by reference.

FIG. 19B further illustrates an embodiment of the sensing unit 1601. Inthis embodiment, the sensing unit 1601 includes 32 sensor coils 1602;each coil 1602 is associated with a separate channel 1606 (shownindividually as channels “Ch 0” through “Ch 31”). The overall dimensionof the panel 1604 can be approximately 40 cm by 54 cm, but the array1605 has a first dimension D1 of approximately 40 cm and a seconddimension D2 of approximately 40 cm. The array 1605 can have other sizesor other configurations (e.g., circular) in alternative embodiments.Additionally, the array 1605 can have more or fewer coils, such as 8-64coils; the number of coils may moreover be a power of 2.

The coils 1602 may be conductive traces or depositions of copper oranother suitably conductive metal formed on the panel 1604. Each coil1602 has a trace with a width of approximately 0.15 mm and a spacingbetween adjacent turns within each coil of approximately 0.13 mm. Thecoils 1602 can have approximately 15 to 90 turns, and in specificapplications each coil has approximately 40 turns. Coils with less than15 turns may not be sensitive enough for some applications, and coilswith more than 90 turns may lead to excessive voltage from the sourcesignal during excitation and excessive settling times resulting from thecoil's lower self-resonant frequency. In other applications, however,the coils 1602 can have less than 15 turns or more than 90 turns.

As shown in FIG. 19B, the coils 1602 are arranged as square spirals,although other configurations may be employed, such as arrays ofcircles, interlocking hexagons, triangles, etc. Such square spiralsutilize a large percentage of the surface area to improve the signal tonoise ratio. Square coils also simplify design layout and modeling ofthe array compared to circular coils; for example, circular coils couldwaste surface area for linking magnetic flux from the markers 40. Thecoils 1602 have an inner dimension of approximately 40 mm, and an outerdimension of approximately 62 mm, although other dimensions are possibledepending upon applications. Sensitivity may be improved with an innerdimension as close to an outer dimension as possible given manufacturingtolerances. In several embodiments, the coils 1602 are identical to eachother or at least configured substantially similarly.

The pitch of the coils 1602 in the array 1605 is a function of, at leastin part, the minimum distance between the marker and the coil array. Inone embodiment, the coils are arranged at a pitch of approximately 67mm. This specific arrangement is particularly suitable when the wirelessmarkers 40 are positioned approximately 7-27 cm from the sensor assembly1012. If the wireless markers are closer than 7 cm, then the sensingsubsystem may include sensor coils arranged at a smaller pitch. Ingeneral, a smaller pitch is desirable when wireless markers are to besensed at a relatively short distance from the array of coils. The pitchof the coils 1602, for example, is approximately 50%-200% of the minimumdistance between the marker and the array.

In general, the size and configuration of the array 1605 and the coils1602 in the array depend on the frequency range in which they are tooperate, the distance from the markers 40 to the array, the signalstrength of the markers, and several other factors. Those skilled in therelevant art will readily recognize that other dimensions andconfigurations may be employed depending, at least in part, on a desiredfrequency range and distance from the markers to the coils.

The array 1605 is sized to provide a large aperture to measure themagnetic field emitted by the markers. It can be particularlychallenging to accurately measure the signal emitted by an implantablemarker that wirelessly transmits a marker signal in response to awirelessly transmitted energy source because the marker signal is muchsmaller than the source signal and other magnetic fields in a room(e.g., magnetic fields from CRTs, etc.). The size of the array 1605 canbe selected to preferentially measure the near field of the marker whilemitigating interference from far field sources. In one embodiment, thearray 1605 is sized to have a maximum dimension D1 or D2 across thesurface of the area occupied by the coils that is approximately 100% to300% of a predetermined maximum sensing distance that the markers are tobe spaced from the plane of the coils. Thus, the size of the array 1605is determined by identifying the distance that the marker is to bespaced apart from the array to accurately measure the marker signal, andthen arrange the coils so that the maximum dimension of the array isapproximately 100% to 300% of that distance. The maximum dimension ofthe array 1605, for example, can be approximately 200% of the sensingdistance at which a marker is to be placed from the array 1605. In onespecific embodiment, the marker 40 has a sensing distance of 20 cm andthe maximum dimension of the array of coils 1602 is between 20 cm and 60cm, and more specifically 40 cm.

A coil array with a maximum dimension as set forth above is particularlyuseful because it inherently provides a filter that mitigatesinterference from far field sources. As such, one aspect of severalembodiments of the invention is to size the array based upon the signalfrom the marker so that the array preferentially measures near fieldsources (i.e., the field generated by the marker) and filtersinterference from far field sources.

The coils 1602 are electromagnetic field sensors that receive magneticflux produced by the wireless markers 40 and in turn produce a currentsignal representing or proportional to an amount or magnitude of acomponent of the magnetic field through an inner portion or area of eachcoil. The field component is also perpendicular to the plane of eachcoil 1602. Each coil represents a separate channel, and thus each coiloutputs signals to one of 32 output ports 1606. A preamplifier,described below, may be provided at each output port 1606. Placingpreamplifiers (or impedance buffers) close to the coils minimizescapacitive loading on the coils, as described herein. Although notshown, the sensing unit 1601 also includes conductive traces orconductive paths routing signals from each coil 1602 to itscorresponding output port 1606 to thereby define a separate channel. Theports in turn are coupled to a connector 1608 formed on the panel 1604to which an appropriately configured plug and associated cable may beattached.

The sensing unit 1601 may also include an onboard memory or othercircuitry, such as shown by electrically erasable programmable read-onlymemory (EEPROM) 1610. The EEPROM 1610 may store manufacturinginformation such as a serial number, revision number, date ofmanufacture, and the like. The EEPROM 1610 may also store per-channelcalibration data, as well as a record of run-time. The run-time willgive an indication of the total radiation dose to which the array hasbeen exposed, which can alert the system when a replacement sensingsubsystem is required.

Although shown in one plane only, additional coils or electromagneticfield sensors may be arranged perpendicular to the panel 1604 to helpdetermine a three-dimensional location of the wireless markers 40.Adding coils or sensors in other dimensions could increase the totalenergy received from the wireless markers 40, but the complexity of suchan array would increase disproportionately. The inventors have foundthat three-dimensional coordinates of the wireless markers 40 may befound using the planar array shown in FIG. 19A-B.

Implementing the sensor assembly 1012 may involve severalconsiderations. First, the coils 1602 may not be presented with an idealopen circuit. Instead, they may well be loaded by parasitic capacitancedue largely to traces or conductive paths connecting the coils 1602 tothe preamplifiers, as well as a damping network (described below) and aninput impedance of the preamplifiers (although a low input impedance ispreferred). These combined loads result in current flow when the coils1602 link with a changing magnetic flux. Any one coil 1602, then, linksmagnetic flux not only from the wireless marker 40, but also from allthe other coils as well. These current flows should be accounted for indownstream signal processing.

A second consideration is the capacitive loading on the coils 1602. Ingeneral, it is desirable to minimize the capacitive loading on the coils1602. Capacitive loading forms a resonant circuit with the coilsthemselves, which leads to excessive voltage overshoot when theexcitation source 1010 is energized. Such a voltage overshoot should belimited or attenuated with a damping or “snubbing” network across thecoils 1602. A greater capacitive loading requires a lower impedancedamping network, which can result in substantial power dissipation andheating in the damping network.

Another consideration is to employ preamplifiers that are low noise. Thepreamplification can also be radiation tolerant because one applicationfor the sensor assembly 1012 is with radiation therapy systems that uselinear accelerators (LINAC). As a result, PNP bipolar transistors anddiscrete elements may be preferred. Further, a DC coupled circuit may bepreferred if good settling times cannot be achieved with an AC circuitor output, particularly if analog to digital converters are unable tohandle wide swings in an AC output signal.

FIG. 20, for example, illustrates an embodiment of a snubbing network1702 having a differential amplifier 1704. The snubbing network 1702includes two pairs of series coupled resistors and a capacitor bridgingtherebetween. A biasing circuit 1706 allows for adjustment of thedifferential amplifier, while a calibration input 1708 allows both inputlegs of the differential amplifier to be balanced. The coil 1602 iscoupled to an input of the differential amplifier 1704, followed by apair of high voltage protection diodes 1710. DC offset may be adjustedby a pair of resistors coupled to bases of the input transistors for thedifferential amplifier 1704 (shown as having a zero value). Additionalprotection circuitry is provided, such as ESD protection diodes 1712 atthe output, as well as filtering capacitors (shown as having a 10 nFvalue).

c. Signal Processors and Controllers

The signal processor 1014 and the controller 1016 illustrated in FIG. 10receive the signals from the sensor assembly 1012 and calculate theabsolute positions of the markers 40 within the reference frame.Suitable signal processing systems and algorithms are set forth in U.S.application Ser. Nos. 10/679,801; 10/749,478; 10/750,456; 10/750,164;10/750,165; 10/749,860; and 10/750,453, all of which are incorporatedherein by reference.

EXAMPLE

Overview

An experimental phantom based study was conducted to determineeffectiveness of this system for real-time tracking. In this experiment,a custom 4D stage was constructed to allow arbitrary motion in threeaxes for speeds up to 10 cm/sec in each dimension, with accuracy to 0.3mm. Position accuracy was measured by a 3D digitizing arm attached tothe stage system. As shown in FIG. 21, two ellipses were created withpeak to peak motion of 2 cm, 4 cm and 2 cm; and 1 cm by 2 cm and 1 cm inthe x, y and z direction respectively. Three periods were used tocorrespond to 15, 17 and 20 breaths per minute. A single transponder wasused with an integration time of 33 ms, 67 ms and 100 ms and twotransponders were used with integration times of 67 ms and 100 ms. Thetransponders were placed in a custom phantom mounted to the 4D stage.The experiment was performed with the isocenter placed 14 cm from the ACmagnetic array to simulate the position of an average lung cancerpatient. The 4D stage ran each trajectory while the real time trackingsystem measured the transponder positions. Measured position wascompared against the phantom position. The effects of ellipse size,speed, transponder number and integration time were characterized.

Experiment Summary

As shown in FIG. 22, the root mean square (RMS) error was less than 1 mmfor each ellipse, period and transponder integration time. The systemwas able to track points throughout the path of the ellipse, forexample, in a trajectory of a large ellipse moving at 17 breaths perminute. FIG. 23 is a histogram of localization errors illustrating thatthe range of error was low for each point measured. As shown in FIG. 24,the RMS error was higher in areas of increased velocity in mosttrajectories. With respect to this experiment, a single transpondersystem performed slightly better than dual transponder systems, with thebest system being a single transponder with a 67 ms integration time.

CONCLUSION

The above description of illustrated embodiments, including what isdescribed in the Abstract, is not intended to be exhaustive or to limitthe invention to the precise forms disclosed. Although specificembodiments of and examples are described herein for illustrativepurposes, various equivalent modifications can be made without departingfrom the spirit and scope of the invention, as will be recognized bythose skilled in the relevant art. The teachings provided herein of theinvention can be applied to target locating and tracking systems, notnecessarily the exemplary system generally described above.

The various embodiments described above can be combined to providefurther embodiments. All of the U.S. patents, U.S. patent applicationpublications, U.S. patent applications, foreign patents, foreign patentapplications and non-patent publications referred to in thisspecification and/or listed in the Application Data Sheet, areincorporated herein by reference, in their entirety. Aspects of theinvention can be modified, if necessary, to employ systems, devices andconcepts of the various patents, applications and publications toprovide yet further embodiments of the invention.

These and other changes can be made to the invention in light of theabove-detailed description. In general, in the following claims, theterms used should not be construed to limit the invention to thespecific embodiments disclosed in the specification and the claims, butshould be construed to include all target locating and monitoringsystems that operate in accordance with the claims to provide apparatusand methods for locating, monitoring, and/or tracking the position of aselected target within a body. Accordingly, the invention is notlimited, except as by the appended claims.

1. In medical applications, a method for tracking a target in a humanpatient using a marker secured in the patient such that the marker issubstantially fixed relative to the target, the method comprising:collecting position data of the marker; determining the location of themarker in an external reference frame based on the position data; andproviding an objective output in the external reference frame that is(a) responsive to the location of the marker and (b) provided at afrequency such that the tracking error is less than 5 mm.
 2. The methodof claim 1 wherein the marker comprises a small transponder thatwirelessly transmits a location signal in response to a wirelesslytransmitted non-ionizing excitation energy, and wherein collecting theposition data comprises sensing the location signal.
 3. The method ofclaim 2 wherein the marker is configured to be implanted in the patient,and wherein the method further comprises implanting the marker at a siteat least proximate to the target such that the marker moves in directcorrelation to movement of the target.
 4. The method of claim 1 whereinthe marker comprises a small leadless marker configured to be implantedin the patient and having a transponder that wirelessly transmits alocation signal in response to a wirelessly transmitted non-ionizingexcitation energy, and wherein the method comprises implanting themarker and collecting the position data comprises sensing the locationsignal.
 5. The method of claim 1 wherein the marker comprises a smallalternating magnetic transponder that wirelessly transmits analternating magnetic location signal in response to a wirelesslytransmitted alternating magnetic field, and wherein collecting theposition data comprises sensing the alternating magnetic locationsignal.
 6. The method of claim 1 wherein the objective output isprovided without human interpretation of at least one of the positiondata and the determined location of the marker.
 7. The method of claim 1wherein the objective output comprises a three-dimensional coordinate inthe external reference frame.
 8. The method of claim 1 wherein theobjective output comprises an offset value between the target and adesired location for the target that is determined in a computer system.9. The method of claim 1 wherein the position data is collected at atime t_(n), and wherein providing the objective output responsive to thelocation of the target comprises providing the objective output to atleast one of a user interface, a memory device, a computer and a medicaldevice within a latency period of not greater than approximately 5seconds of time t_(n) and at a periodicity not greater thanapproximately 15 seconds.
 10. The method of claim 9 wherein the latencyperiod is not greater than approximately 2 seconds of time t_(n) and ata periodicity not greater than approximately 2 seconds.
 11. The methodof claim 9 wherein the latency period is not greater than approximately1 second of time t_(n) and at a periodicity not greater thanapproximately 1 second.
 12. The method of claim 9 wherein the latencyperiod is not greater than approximately 100 ms of time t_(n) and at aperiodicity not greater than approximately 200 ms.
 13. The method ofclaim 9 wherein the latency period is not greater than approximately 50ms of time t_(n) and at a periodicity not greater than approximately 50ms.
 14. The method of claim 9 wherein the periodicity is approximately12.5 ms.
 15. The method of claim 9 wherein the periodicity isapproximately 16.67 ms.
 16. The method of claim 9 wherein theperiodicity is approximately 20 ms.
 17. The method of claim 1, furthercomprising positioning the patient to locate the target at a desiredlocation relative to an isocenter of a radiation delivery device whileperforming the collecting, determining and providing procedures.
 18. Themethod of claim 1, further comprising irradiating the patient with ahigh-intensity ionizing beam directed to an isocenter of a radiationdelivery device while performing the collecting, determining andproviding procedures.
 19. The method of claim 18, further comprisingcontrolling at least one of a patient position and a parameter of thehigh-intensity ionizing beam while performing the collecting,determining and providing procedures.
 20. The method of claim 19,further comprising controlling an on-off state of the non-ionizing beamsuch that the non-ionizing beam is on when the target is indicated asbeing located at a desired position relative to the machine isocenter.21. The method of claim 19, further comprising moving the patient toposition the target at a desired location relative to the machineisocenter.
 22. The method of claim 19, further comprising changing ashape of the non-ionizing beam.
 23. The method of claim 1 whereinproviding the objective output in the external reference frame comprisesproviding the objective output at least substantially contemporaneouslywith collecting the position data used to determine the location of themarker.
 24. The method of claim 1 wherein the frequency comprisesproviding a plurality of objective outputs during a beam-on period. 25.In radiation therapy for treating a target within a patient, a methodfor tracking the target in real time using a marker implanted in thepatient at a site relative to the target, the method comprising:collecting position data of the marker at a time t_(n); determining thelocation of the marker in an external reference frame based on theposition data; providing an objective output indicative of the locationof the target to a user interface, a memory device and/or a radiationdelivery device within a latency not greater than 2 seconds of timet_(n); repeating the providing procedure at least every 2 seconds. 26.The method of claim 25 wherein the marker comprises a small transponderthat wirelessly transmits a location signal in response to a wirelesslytransmitted non-ionizing excitation energy, and wherein collecting theposition data comprises sensing the location signal wirelesslytransmitted by the marker.
 27. The method of claim 25 wherein the markercomprises a small alternating magnetic transponder that wirelesslytransmits an alternating magnetic location signal in response to awirelessly transmitted alternating magnetic field, and whereincollecting the position data comprises sensing the alternating magneticlocation signal wirelessly transmitted by the marker.
 28. The method ofclaim 25 wherein the objective output comprises an offset coordinatebetween the location of the target and an isocenter of the radiationdelivery device.
 29. The method of claim 28 wherein providing theobjective output comprises sending the offset coordinate to the userinterface, the memory device and/or the radiation delivery device withina latency of approximately 1 ms to approximately 1 second of time t_(n)and at a periodicity of approximately 1 ms to approximately 1 second.30. The method of claim 28 wherein providing the objective outputcomprises sending the offset coordinate to the user interface, thememory device and/or the radiation delivery device within a latency ofapproximately 1 ms to approximately 100 ms of time t_(n) and at aperiodicity of approximately 1 ms to approximately 200 ms.
 31. Themethod of claim 28 wherein providing the objective output comprisessending the offset coordinate to the user interface, the memory deviceand/or the radiation delivery device within a latency of approximately10 ms to approximately 50 ms of time t_(n) and at a periodicity ofapproximately 20 ms to approximately 50 ms.
 32. The method of claim 25wherein the objective output comprises a coordinate in the externalreference frame related to the location of the target, and whereinproviding the objective output comprises sending the coordinate to theuser interface within a latency of approximately 10 ms to approximately100 ms of time t_(n) and at a periodicity of approximately 10 ms toapproximately 50 ms.
 33. The method of claim 32 wherein the periodicityis approximately 12.5 ms.
 34. The method of claim 32 wherein theperiodicity is approximately 16.67 ms.
 35. The method of claim 32wherein the periodicity is approximately 20 ms.
 36. The method of claim25, further comprising positioning the patient to locate the target at adesired location relative to an isocenter of the radiation deliverydevice while performing the collecting, determining and providingprocedures.
 37. The method of claim 36 wherein the objective outputcomprises an offset coordinate between the location of the target and adesired site for the target relative to the isocenter of the radiationdelivery device, and wherein providing the objective output comprisessending the offset coordinate to the user interface, the memory deviceand/or the radiation delivery device within a latency of approximately 1ms to approximately 100 ms of time t_(n) and at a periodicity ofapproximately 1 ms to approximately 200 ms.
 38. The method of claim 37wherein providing the objective output comprises sending the offsetcoordinate to the user interface within a latency of approximately 10 msto approximately 100 ms of time t_(n) and at a periodicity ofapproximately 10 ms to approximately 50 ms.
 39. The method of claim 37wherein providing the objective output comprises sending the offsetcoordinate to the radiation delivery device within a latency ofapproximately 1 ms to approximately 100 ms of time t_(n) and at aperiodicity of approximately 1 ms to approximately 50 ms, and whereinthe radiation delivery device automatically moves a patient supporttable according to the offset coordinate.
 40. The method of claim 25,further comprising irradiating the target with a radiation beam from theradiation delivery device while performing the collecting, determiningand providing procedures.
 41. The method of claim 40 wherein theobjective output comprises an offset coordinate between the location ofthe target and a desired site for the target relative to an isocenter ofthe radiation delivery device, and wherein providing the objectiveoutput comprises sending the offset coordinate to the radiation deliverydevice within a latency of approximately 1 ms to approximately 100 ms oftime t_(n) and at a periodicity of approximately 1 ms to approximately200 ms.
 42. The method of claim 41, further comprises controlling aparameter of the radiation delivery device according to the offsetcoordinate.
 43. The method of claim 42 wherein controlling the parameterof the radiation delivery device comprises terminating the radiationbeam when the offset coordinate exceeds a predetermined value indicatingthat the target is outside of an acceptable range of the isocenter. 44.The method of claim 42 wherein controlling the parameter of theradiation delivery device comprises automatically moving a patientsupport table according to the offset coordinate.
 45. In radiationtherapy for treating a target in a patient, a method of tracking thetarget, comprising: obtaining position data of a marker situated withinthe patient at a site relative to the target; determining a location ofthe marker in an external reference frame based on the position data;and providing to a user interface an objective output indicative of thelocation of the target based on the determined location of the marker at(a) a sufficiently high frequency so that pauses in representations ofthe target location at the user interface are not readily discernable bya human and (b) a sufficiently low latency to be at least substantiallycontemporaneous with obtaining the position data of the marker.
 46. Themethod of claim 45 wherein the marker comprises a small transponder thatwirelessly transmits a location signal in response to a wirelesslytransmitted non-ionizing excitation energy, and wherein obtaining theposition data comprises sensing the location signal wirelesslytransmitted from the marker.
 47. The method of claim 45 wherein themarker comprises a small alternating magnetic transponder thatwirelessly transmits an alternating magnetic location signal in responseto a wirelessly transmitted alternating magnetic field, and whereinobtaining the position data comprises sensing the alternating magneticlocation signal wirelessly transmitted by the marker.
 48. The method ofclaim 45 wherein the position data is obtained at a time t_(n) and theobjective output comprises an offset coordinate between the location ofthe target and a desired site for the target relative to an isocenter ofa radiation delivery device.
 49. The method of claim 48 whereinproviding the objective output comprises sending the offset coordinateto the user interface and/or the radiation delivery device within alatency of approximately 1 ms to approximately 1 second of time t_(n)and at a periodicity of approximately 1 ms to approximately 1 second.50. The method of claim 48 wherein providing the objective outputcomprises sending the offset coordinate to the user interface and/or theradiation delivery device within a latency of approximately 1 ms toapproximately 100 ms of time t_(n) and at a periodicity of approximately1 ms to approximately 200 ms.
 51. The method of claim 48 whereinproviding the objective output comprises sending the offset coordinateto the user interface and/or the radiation delivery device within alatency of approximately 10 ms to approximately 50 ms of time t_(n) andat a periodicity of approximately 20 ms to approximately 50 ms.
 52. Themethod of claim 45 wherein the position data is obtained at a time t_(n)and the objective output comprises a coordinate in the externalreference frame related to the location of the target, and whereinproviding the objective output comprises sending the coordinate to theuser interface within a latency of approximately 10 ms to approximately100 ms of time t_(n) and at a periodicity of approximately 10 ms toapproximately 50 ms.
 53. The method of claim 45, further comprisingpositioning the patient to locate the target at a desired locationrelative to an isocenter of a radiation delivery device while performingthe obtaining, determining and providing procedures.
 54. The method ofclaim 45 wherein the position data is obtained at a time t_(n) and theobjective output comprises an offset coordinate between the location ofthe target and a desired site for the target relative to the isocenterof the radiation delivery device, and wherein providing the objectiveoutput comprises sending the offset coordinate to the user interfaceand/or the radiation delivery device within a latency of approximately 1ms to approximately 100 ms of time t_(n) and at a periodicity ofapproximately 1 ms to approximately 200 ms.
 55. The method of claim 54wherein providing the objective output comprises sending the offsetcoordinate to the user interface within a latency of approximately 10 msto approximately 100 ms of time t_(n) and at a periodicity ofapproximately 10 ms to approximately 50 ms.
 56. The method of claim 54wherein providing the objective output comprises sending the offsetcoordinate to the radiation delivery device within a latency ofapproximately 1 ms to approximately 100 ms of time t_(n) and at aperiodicity of approximately 1 ms to approximately 50 ms, and whereinthe radiation delivery device moves a patient support table according tothe offset coordinate.
 57. The method of claim 45, further comprisingirradiating the target with a radiation beam from a radiation deliverydevice while performing the obtaining, determining and providingprocedures.
 58. The method of claim 57 wherein the position data isobtained at a time t_(n) and the objective output comprises an offsetcoordinate between the location of the target and a desired site for thetarget relative to an isocenter of the radiation delivery device, andwherein providing the objective output comprises sending the offsetcoordinate to the radiation delivery device within a latency ofapproximately 1 ms to approximately 100 ms of time t_(n) and at aperiodicity of approximately 1 ms to approximately 200 ms.
 59. Themethod of claim 58, further comprises controlling a parameter of theradiation delivery device according to the offset coordinate.
 60. Themethod of claim 59 wherein controlling a parameter of the radiationdelivery device comprises terminating a radiation beam when the offsetcoordinate exceeds a predetermined value indicating that the target isoutside of an acceptable range of the isocenter.
 61. The method of claim59 wherein controlling a parameter of the radiation delivery devicecomprises automatically moving a patient support table according to theoffset coordinate.
 62. A radiation therapy system for treating a targetof a patient using a marker implanted in the patient at a site relativeto the target, the system comprising: a radiation delivery deviceincluding a beam generator for generating a beam of ionizing radiation,an isocenter, and an aiming system for directing the beam to theisocenter; a detector that obtains position data of the marker at a timet_(n); and a computer operatively coupled to the detector to receive theposition data, the computer having a computer operable medium thatdetermines a location of the marker based on the position data andprovides an objective output indicative of a location of the target to auser interface, a memory device, and/or a radiation delivery devicewithin a latency of not greater than 2 seconds from time t_(n) and at aperiodicity of not greater than 2 seconds.
 63. The radiation therapysystem of claim 62, further comprising an excitation source configuredto wirelessly transmit a non-ionizing excitation energy, a marker havinga small transponder configured to wirelessly transmit a location signalin response to the wirelessly transmitted non-ionizing excitationenergy, and wherein the detector is configured to sense the locationsignal wirelessly transmitted by the marker.
 64. The radiation therapysystem of claim 62, further comprising an excitation source configuredto wirelessly transmit an alternating magnetic field, a marker having asmall alternating magnetic transponder that wirelessly transmits analternating magnetic location signal in response to the wirelesslytransmitted alternating magnetic field, and wherein the detectorcomprises a coil configured to sense the alternating magnetic locationsignal wirelessly transmitted by the marker.
 65. The radiation therapysystem of claim 62 wherein the objective output comprises an offsetcoordinate between the location of the target and a desired site for thetarget relative to an isocenter of the radiation delivery device. 66.The radiation therapy system of claim 65 wherein the computer-operablemedium sends the offset coordinate to the user interface, the memorydevice and/or the radiation delivery device within a latency ofapproximately 1 ms to approximately 1 second of time t_(n) and at aperiodicity of approximately 1 ms to approximately 1 second.
 67. Theradiation therapy system of claim 65 wherein the computer-operablemedium sends the offset coordinate to the user interface, the memorydevice and/or the radiation delivery device within a latency ofapproximately 1 ms to approximately 100 ms of time t_(n) and at aperiodicity of approximately 1 ms to approximately 200 ms.
 68. Theradiation therapy system of claim 65 wherein the computer-operablemedium sends the offset coordinate to the user interface, the memorydevice and/or the radiation delivery device within a latency ofapproximately 10 ms to approximately 50 ms of time t_(n) and at aperiodicity of approximately 20 ms to approximately 50 ms.
 69. Theradiation therapy system of claim 65 wherein the objective outputcomprises a coordinate in the external reference frame related to thelocation of the target, and wherein the computer-operable medium sendsthe coordinate to the user interface within a latency of approximately10 ms to approximately 100 ms of time t_(n) and at a periodicity ofapproximately 10 ms to approximately 50 ms.
 70. The radiation therapysystem of claim 62, wherein the computer-operable medium sends a signalfor positioning the patient to locate the target at a desired locationrelative to an isocenter of the radiation delivery device.
 71. Theradiation therapy system of claim 70 wherein the objective outputcomprises an offset coordinate between the location of the target and anisocenter of the radiation delivery device, and the computer-operablemedium sends the offset coordinate to the user interface, the memorydevice and/or the radiation delivery device within a latency ofapproximately 1 ms to approximately 100 ms of time t_(n) and at aperiodicity of approximately 1 ms to approximately 200 ms.
 72. Theradiation therapy system of claim 71 wherein the computer-operablemedium sends the offset coordinate to the user interface within alatency of approximately 10 ms to approximately 100 ms of time t_(n) andat a periodicity of approximately 10 ms to approximately 50 ms.
 73. Theradiation therapy system of claim 71 wherein the computer-operablemedium sends the offset coordinate to the radiation delivery devicewithin a latency of approximately 1 ms to approximately 100 ms of timet_(n) and at a periodicity of approximately 1 ms to approximately 50 ms,and wherein the radiation delivery device is configured to automaticallymove a patient support table according to the offset coordinate.
 74. Theradiation therapy system of claim 62 wherein the objective outputcomprises an offset coordinate between the location of the target and anisocenter of the radiation delivery device, and wherein thecomputer-operable medium sends the offset coordinate to the radiationdelivery device within a latency of approximately 1 ms to approximately100 ms of time t_(n) and at a periodicity of approximately 1 ms toapproximately 200 ms.
 75. A tracking system for treating a target of apatient using a marker implanted in the patient at a site relative tothe target, the system comprising: a detector that obtains position dataof the marker at a time t_(n); and a computer operatively coupled to thedetector to receive the position data, the computer having a computeroperable medium that determines a location of the marker based on theposition data and provides an objective output indicative of a locationof the target within a latency of 10-200 ms from time t_(n) and at aperiodicity of 10-100 ms.
 76. A method of treating a target of a patientwith an ionizing radiation, comprising: generating a beam of ionizingradiation and directing the beam relative to the target; collectingposition information of a marker implanted within a patient at a siterelative to the target while directing the beam toward the beamisocenter; providing an objective output indicative of a location of thetarget relative to the beam isocenter based on the collected positioninformation; and correlating the objective output with a parameter ofthe beam.
 77. A method of treating a target of a patient with anionizing radiation, comprising: generating a beam of ionizing radiationand directing the beam relative to the target with a multi-leafcollimator; collecting position information of a marker implanted withina patient at a site relative to the target while directing the beamtoward the beam isocenter; and providing an objective output indicativeof a location of the target of the patient based on the collectedposition information relative to the beam isocenter and controlling aconfiguration of the multi-leaf collimator based on the objectiveoutput.
 78. A method of treating a target of a patient with an ionizingradiation, comprising: generating a beam of ionizing radiation anddirecting the beam relative to the target; and operating a localizationsystem to (a) collect position information of a marker implanted withina patient at a site relative to the target while directing the beamtoward the beam isocenter and (b) provide an objective output indicativeof a location of the target relative to the beam isocenter based on thecollected position information of the marker while directing the beamtoward the beam isocenter for a period of at least 10 seconds withoutrecalibrating the localization system.